Optogenetic activation of mGluR1 signaling in the cerebellum induces synaptic plasticity.

Neuronal plasticity underlying cerebellar learning behavior is strongly associated with type 1 metabotropic glutamate receptor (mGluR1) signaling. Activation of mGluR1 leads to activation of the Gq/11 pathway, which is involved in inducing synaptic plasticity at the parallel fiber-Purkinje cell synapse (PF-PC) in form of long-term depression (LTD). To optogenetically modulate mGluR1 signaling we fused mouse melanopsin (OPN4) that activates the Gq/11 pathway to the C-termini of mGluR1 splice variants (OPN4-mGluR1a and OPN4-mGluR1b). Activation of both OPN4-mGluR1 variants showed robust Ca2+ increase in HEK cells and PCs of cerebellar slices. We provide the prove-of-concept approach to modulate synaptic plasticity via optogenetic activation of OPN4-mGluR1a inducing LTD at the PF-PC synapse in vitro. Moreover, we demonstrate that light activation of mGluR1a signaling pathway by OPN4-mGluR1a in PCs leads to an increase in intrinsic activity of PCs in vivo and improved cerebellum driven learning behavior.

Prospective, Randomized Comparative Evaluation of a Novel Hands-On Endourology Training Curriculum.

INTRODUCTION: The aim of this randomised prospective trial was to evaluate a novel hands-on endourological training programme (HTP) and compare it to the standard endourological colloquium (SC). METHODS: A new HTP was created based on a sequence of theoretical, video-based, and practical elements emphasising contemporary teaching methods. An existing SC in which live endourological operations were attended served as a comparison. Medical students were enrolled in a ratio of 1:2 (SC:HTP). Objective knowledge questionnaires (5 questions, open answers) and subjective Likert-type questionnaires (rating 1-3 vs. 4-5) were used for evaluation. Primary endpoint was urological knowledge transfer; secondary endpoints were learning effects, progression, and urological interest. RESULTS: 167 students (SC n = 52, HTP n = 115) were included. The knowledge assessment showed a significant increase in knowledge transfer benefitting the HTP on all 5 surveyed items (mean: n = 4/5/4/3/2 vs. n = 2/3/1/1, p < 0.0001). Interest and duration of the course were rated significantly more positively by HTP students (100.0/95.0% vs. 85.0/70.0%, p < 0.0001). The HTP students were significantly more confident in performing a cystoscopy independently (HTP 43.5% vs. SC 11.5%, p < 0.0001) and significantly claimed more often to have gained interdisciplinary and urological skills during the course (HTP 90.0/96.5% vs. SC 23.1/82.7%, p < 0.0001/p = 0.003). HTP students were also more likely to take the course again (HTP 98.2% vs. SC 59.6%, p < 0.0001). CONCLUSION: Modifying endourological teaching towards hands-on teaching resulted in stronger course interest, greater confidence regarding endourologic procedures, and significantly increased urologic knowledge transfer.

Endourological Training Using 3D-Printed Bladder Phantoms: Development and Prospective Evaluation.

Background: To create and evaluate a realistic, anatomically accurate, and user-friendly bladder phantom for reproducible endourological training purposes and endoscope mastery. Materials and Methods: The anatomy of full bladders was mapped from human computed tomography datasets. After a 3D model development process, content evidence and response process evidence (RPE) of the phantom were evaluated using the system usability scale (SUS), 5-point Likert scale questionnaires, and task execution of experienced urologists (U) and endoscopy-naive medical students (MS) in two training sessions (first vs second). Required validation cohort sizes (1:10) of the evaluating urologists (n = 12) and students (n = 115) were precalculated. Time measurements were recorded. Students were additionally evaluated by a validated global psychomotor assessment score (GPSS). Group comparisons were calculated by the Mann-Whitney U test. All tests were two sided with p < 0.05 considered statistically significant. Results: Content evidence was assessed by urologists with an "excellent" SUS score of 89.4 ± 5.9 and an average "agreement" of ≥4 pts in the Likert scale questionnaires. RPE was assessed by intra- and intergroup time comparison for the execution of endoscopic tasks (cystoscopy [CY], guidewire insertion, and tumor biopsy). For CY, U: first 17.6 ± 4.4 seconds vs second 12.4 ± 2.0 seconds, p = 0.002; MS: first 56.6 ± 28.2 seconds vs second 28.6 ± 14.7 seconds, p < 0.001; U vs MS: first U 17.6 ± 4.4 seconds vs first MS 56.6 ± 28.2 seconds, p < 0.001, second U 12.4 ± 2.0 seconds vs second MS 28.6 ± 14.7 seconds, p < 0.001. Significant time differences were documented for all tasks and sessions (p < 0.001). Additionally, significant GPSS differences were recorded between the sessions (GPSS: first 20.4 ± 5.1 pts vs second 24.7 ± 4.0 pts, p < 0.001). Conclusions: Our low-fidelity 3D-printed bladder, called BladCap, is an easy-to-assemble, inexpensive, and robust phantom. We present data, which establish construct validity to support use as a clinical training device.

Preclinical and Clinical Evaluation of a Novel, Variable-View, Rigid Endoscope for Female Cystoscopy.

OBJECTIVE: To evaluate the preclinical and clinical performance of the pivoting lens rigid Endocameleon (ECAM) endoscope in white light cystoscopy (WLC). MATERIALS AND METHODS: Preclinical evaluation was performed ex vivo in CT-based, anatomically accurate and validated bladder phantoms. Six defined tasks with objective endpoints were compared between ECAM-WLC and rigid WLC (30° view angle, rWLC) in 30 interventions. Subsequently, the comparison was transferred to in vivo n = 21 interventions. A validated usability score (System Usability Scale, SUS) as well as physician and patient-related outcomes were assessed using Likert-scale-based questionnaires. Intra- and postinterventional complications were recorded according to the Clavien-Dindo classification. RESULTS: The ex vivo evaluation showed a significant superiority of ECAM-WLC in 4 of 6 endoscopic tasks. Noteworthy is the lower pressure on the bladder neck due to the endoscopesalteration of the endoscope (4/60 vs 17/60, P <.0001) and a more precise imaging of all bladder regions (22/30 vs 30/30, P = .046), including the anterior wall (0/30 vs 28/30, P <.0001). In vivo, surgeons rated the ECAM-WLC with an "excellent" SUS of 86.79%, also expressing that ECAM-WLC would enhance bladder surface visualization (4.52/5.0 ± 0.51), with a preferred use for ECAM-WLC during their next cystoscopy (4.62 ± 0.50). Patients reported ECAM-WLC to be less painful (4.5/5.0 ± 0.84) compared to rWLC. No intervention-related complications were observed. CONCLUSION: ECAM-WLC is a safe and accessible procedure that could improve conventional diagnostic WLC by combination of the advantages of fWLC and rWLC.